tbuckley/cabot-search huggingface dataset:
Prostate cancer public health system database from Brazil: Racial disparities and heterogeneity of treatment interventions to understand evidence-based practice patterns in a large real-world database.
Authors: Daniel Herchenhorn, Rana R. McKay, Andre Deeke Sasse, Fernando Sabino Marques Monteiro, Brent Shane Rose, Gustavo Carvalhal, Fernando Cotait Maluf, Igor Alexandre Protzner Morbeck, Vinicius Carrera Souza, Elcio Firminiano Fernandes, Douglas Andreas Valverde, Nicholas D. James
Journal: Journal of Clinical Oncology (2023)

5025 Background: The Brazilian Public National Health System (SUS) provides an opportunity to understand epidemiologic information, treatments, discrepancies in care, and costs of men with prostate cancer (PCa) using a large real-world dataset. This analysis focuses on racial disparities and heterogeneity of specific interventions to understand evidence-based practice patterns in Brazil. Additionally, the dataset can serve as a model for other low-middle income countries (LMIC). Methods: Patients included in the database were those with a diagnosis of PCa receiving care in the SUS from 01/01/2008 to 08/31/2022. Data were analyzed using a proprietary Healthcare Data Science platform offered by TECHTRIALS and included information regarding stage, demographics, cancer-related information, treatment-related information, and resources utilized. Results: 657,609 PCa pts were diagnosed and treated at SUS during the 14.5-year study period of whom 382,263 (58%) were brown/black (non-white) and 262,820 (42%) white. Median age of the population was 72.6 years, and did not vary with race. 26.16% of the pts were diagnosed with stage IV and this was not impacted by race or localization, including state or type of city (capital or not). Rates of radical prostatectomy and radiation utilization were similar between race categories. Additionally, in patients with stage IV disease, rates of systemic therapy utilization including chemotherapy with docetaxel (7.7%), with a tendency to increase use in the last years, and androgen receptor signaling inhibitors (ARSI) with (0.6%) or enzalutamide (0.08%), were low and similar between race categories. Rates of first-generation anti-androgens and estrogens were higher (56%) The total costs of prostate cancer directed care was R$4.31 billions (US$820 millions) and race did not impact total cost of care and cost by procedure or therapy type options. Conclusions: This is one of the largest studies using public health-system databases for Prostate cancer with Real World Data ever published. Race had no impact in presenting stage, treatment received and even in the costs involved. Underutilization of chemotherapy (docetaxel) in a scenario of limiting resources and without the use of new hormonal therapies is a matter of concern, together with an overuse of agents without proven survival advantage. Our data highlights the need for increased access to life prolonging agents for patients with metastatic PCa in the SUS.
Association of CDK4 amplification with duration of response to bevacizumab in glioblastoma.
Authors: John L. Villano, Rachael M Morgan, Shulin Zhang, Jill Kolesar, Joanne Xiu, Hilary Seifert, Theodore Nicolaides, Stephanie Rock, Santosh Kesari, Sonikpreet Aulakh, Eric T. Wong, Michael J. Glantz
Journal: Journal of Clinical Oncology (2023)

2026 Background: Bevacizumab remains the standard second line therapy in glioblastoma (GBM) with reported improved progression free survival, but not overall survival. We investigated a large clinico-genomic database of GBM patients treated with bevacizumab for molecular alterations associated with treatment outcome. Methods: Molecular profiles of GBM were tested by next-generation sequencing (NGS) of DNA (592 genes, NextSeq or whole-exome sequencing, Novaseq) and RNA (whole transcriptome sequencing, NovaSeq) at Caris Life Sciences (Phoenix, AZ). Gene amplification was determined by NGS with a threshold of &gt; = 6 copies. Real-world survival information was obtained from insurance claims data. Time-on-treatment (TOT) of bevacizumab was calculated from start to finish of treatment while post-bevacizumab overall survival (bevOS) from start of bevacizumab to last day of contact. Short-term (ST) and long-term (LT) responders were defined as those with TOT ≤6 months and ≥1 year, respectively. Kaplan-Meier estimates were calculated and significance was determined as p values of &lt; 0.05. For molecular comparisons, Fisher’s exact tests and Mann-Whiney U were used when appropriate. Results: Among the total of 383 ST and 107 LT patients identified, no significant difference in gender or age were seen. The LT cohort had significantly longer bevOS compared to the ST cohort (HR 0.27, [95% CI: 0.28-0.35], p &lt; 0.0001). Interestingly, CDK4 amplification was seen in 23% (18/78) of LT patients but only 7% (21/300, p = 0.0002) of ST. When investigating the total cohort of 498 GBM treated with bevacizumab, CDK4 amplified patients demonstrated significantly improved TOT compared to non-amplified (HR: 0.639, [0.48-0.85, p = 0.002]). Conversely, the ST cohort had significantly more EGFR amplifications than the LT cohort (43%, 130/300 vs. 19%, 15/79, p &lt; 0.0001). In the total bevacizumab-treated cohort, EGFR-amplified GBM had significantly worse TOT on bevacizumab than non-EGFR amplified GBM (HR 1.387, [1.15-1.67], p &lt; 0.001). No associations were seen in other alterations explored including PIK3CA mutation (HR = 0.81 [0.587-1.113], p = 0.2), EGFR mutation (HR: 1.209, [0.977-1.495], p = 0.1) or RAF1 (HR: 0.647, [0.318-1.317], p = 0.2). Conclusions: Using a large clinical genomic database with GBM subjected to comprehensive molecular profiling, we demonstrated that amplification of CDK4 and EGFR were associated with long-term and short-term responses to bevacizumab, respectively. This warrants further investigation in independent cohorts controlled for age and other prognostic factors. If confirmed, a genetic basis for treatment optimization may provide meaningful clinical outcomes.
A retrospective study on the efficacy and safety of avatrombopag in the treatment of chemotherapy-induced thrombocytopenia in gastrointestinal cancer.
Authors: Junliang Chen, Wangjun Liao, Lingjun Zhu, Yifu He, Gang Jin, Ying Pan, Fenghua Wang
Journal: Journal of Clinical Oncology (2023)

e16334 Background: Chemotherapy-induced thrombocytopenia (CIT) is defined as post-chemotherapy platelets count &lt; 100×10 9 /L. Avatrombopag is an oral thrombopoietin receptor to treat thrombocytopenia. Although many factors lead to an increased risk of CIT in gastrointestinal cancer, there is currently no targeted research. This study aimed to investigate the efficacy and safety of avatrombopag for CIT in gastrointestinal cancer. Methods: This multicenter, retrospective study included adult gastrointestinal cancer patients with CIT who received avatrombopag treatment (40mg/60mg, 5 days) between September 2020 and February 2022. The patient meets one of the following conditions were included in this study: a) Platelet count &lt;100×10 9 /L before receiving avatrombopag treatment in the current chemotherapy cycle, and platelet count &lt;50×10 9 /L in the last cycle; b) Platelet count &lt;75×10 9 /L before receiving avatrombopag treatment in the current chemotherapy cycle. The main endpoint was the proportion of patients with platelet count &gt;100×10 9 /L or platelet count increased by &gt;50×10 9 /L or platelet count increased by &gt; 100% in the cycle after the start of avatrombopag therapy. Results: 58 patients were included in this study. 53.40%, 82.80%, and 96.6% of the patients reached the effective endpoint after 5±2, 11±3, and 18±3 days of avatrombopag treatment, respectively. No drug toxicity related to avatrombopag was found in this study. No significant influencing factors of effective rate were found. And there was no significant difference was found among the effective rate and platelet transfusion rate of avatrombopag (AVA), AVA+Recombinant Human Interleukin-11 (rhIL-11), and AVA+Recombinant Human Thrombopoietin (rhTPO). However, compared with AVA+IL-11, the AVA+rhTPO group had lower baseline platelet counts. And the mean of increasing platelet counts on the 5±2 (41.32×10 9 /L vs. 37.00×10 9 /L) and 11±3 day (110.94×10 9 /L vs. 84.00×10 9 /L) were better in the AVA+rhTPO group, though not significantly. Conclusions: Avatrombopag has high efficacy and safety in the treatment of CIT in gastrointestinal cancer. rhTPO rather than rhIL-11 combined with avatrombopag may be more suitable for patients with low baseline platelet counts. [Table: see text]
Patterns and outcomes of palliative radiation therapy with immunotherapy in locally recurrent head and neck squamous cell carcinoma.
Authors: Logan Roof, David Buchberger, Anirudh Yalamanchali, Shauna Campbell, Jacob Miller, Shlomo A. Koyfman, Neil McIver Woody, Jessica Lyn Geiger, Emrullah Yilmaz
Journal: Journal of Clinical Oncology (2023)

e18015 Background: Immune checkpoint inhibitors (ICI) have been shown to improve outcomes in patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Radiation therapy (RT) is commonly incorporated into R/M HNSCC treatment for symptom management and disease control. RT is a potential immunostimulatory treatment modality that may enhance the antitumor activity of ICI; however, ideal sequencing of RT and ICI in the palliative treatment setting is not defined. The objective of this study was to describe the patterns and outcomes of RT and ICI in locally recurrent HNSCC. Methods: All adults (≥ 18 years) with HNSCC who received palliative ICI for R/M disease from 2015-2021 were identified from the institutional electronic medical record via ICD codes under an IRB approved protocol. Patients who received ICI for non-HNSCC, had synchronous primary tumors, or had history of hematologic malignancy or immunodeficiency were excluded. Patients without documentation of clinical outcomes after palliative RT were excluded. Retrospective data were collected and underwent descriptive analysis. Results: We identified 26 patients who received palliative ICI and RT for locally recurrent HNSCC. Twelve underwent palliative RT while on ICI. In this group, there were 0 patients with complete response (CR), five with partial response (PR), two with stable disease (SD), and four with progression of disease (PD) in the target lesion. There were 10 grade 3 events. Fourteen patients had RT separately from ICI: 6 before and 8 after receiving ICI. In this group, there was one patient with CR, six with PR, one with SD, and six with PD in the target lesion. There were 3 grade 3 events. Most common grade 3 events in both groups were: dysphagia, mucositis, and voice change. The most common modalities of RT were SBRT, IMRT, and 3D conformal; 7 patients underwent SBRT, 19 underwent IMRT/3D conformal, with similar responses in target lesions. Conclusions: These data suggest that concurrent ICI and palliative RT for locally recurrent HNSCC is effective in the target lesions, but has an increase in toxicities. Although there was a small number of patients who underwent concurrent ICI and RT, the disease control rate (DCR) in this group was 58%, which is promising. Similarly, the DCR for patients receiving ICI and RT separately was 57%. Further study on the optimal type and sequence of palliative RT in this patient population is warranted.
Impact of a web-based decision aid on socioeconomically disadvantaged patients’ engagement in decision making (Alliance A231701CD).
Authors: Jessica R. Schumacher, Bret M Hanlon, David Zahrieh, Paul J Rathouz, Jennifer L Tucholka, Angelina D. Tan, Catherine Breuer, Lisa Bailey, Anna M Higham, Julie Sara Wecsler, Alicia Y Vinyard, Anthony J. Froix, Andrea M. Abbott, Scott Dull, Stephanie G Fine, Kandace P McGuire, Anna S. Seydel, Patricia McNamara, Selina Lai-ming Chow, Heather B. Neuman
Journal: Journal of Clinical Oncology (2023)

6520 Background: Increased patient engagement in decision making may mitigate disparities in breast cancer surgical care. Socioeconomically disadvantaged patients disproportionately experience barriers to engagement. Decision aids (DA) increase engagement by providing information, establishing role expectations during the consult, and increasing confidence in surgeon interactions. The objective was to test the effectiveness of a surgical web-based DA in increasing engagement among breast cancer patients in clinics that care for a high proportion of socioeconomically disadvantaged patients. Methods: A stepped wedge trial was conducted with 10 NCI Community Oncology Research Program clinics (Alliance for Clinical Trials in Oncology Research Base, 6/19-12/21). Clinics were randomized to time of transition from usual care (UC) to delivery of a web-based DA. Patients with stage 0-3 breast cancer eligible for surgery provided consent prior to a surgical consult. Socioeconomic disadvantage was assessed with the Area Deprivation Index measured at the zip+4 level and dichotomized. Patient engagement was measured by Patient’s Self-Efficacy in Patient-Physician Interactions (PEPPI-5, follow-up survey) and count of Active Patient Behaviors (Street protocol, audio recorded consult). Intervention effects were tested with linear mixed-effects models, accounting for surgeon and clinic-level clustering, time, and enrollment post-COVID. Heterogeneity of treatment effect by socioeconomic disadvantage was assessed with an interaction term. Results: 573 patients enrolled. 44% (136/309) reviewed the DA. No significant difference in engagement was observed comparing DA and UC for PEPPI-5 (-0.80 [95% CI -2.13, 0.54], p = 0.24) or Active Patient Behaviors (2.52 [CI -4.11, 9.15], p = 0.46). Enrollment post-COVID was associated with increased Active Patient Behaviors (9.59 [CI 1.76, 17.43], p = 0.02) but no change in PEPPI-5 (-1.31 [CI -2.88, 0.26], p = 0.10). No heterogeneity of treatment effect was observed. Conclusions: In this trial conducted in clinics that serve diverse populations, no significant relationship was observed between a web-based DA and patient engagement. Conducting this stepped wedge trial during the pandemic was challenging. Future analyses will explore the impact of COVID on outcomes and effect of the decision aid for patients who reviewed it. UG1 CA189823; AHRQ R01HS025194; https://acknowledgments.alliancefound.org . Clinical trial information: NCT03766009 . [Table: see text]
A prospective, single-arm, phase II clinical study of tislelizumab in combination with lenvatinib for perioperative treatment of resectable primary hepatocellular carcinoma with high risk of recurrence.
Authors: Tianqiang Song
Journal: Journal of Clinical Oncology (2023)

e16218 Background: Surgery is the main radical treatment for hepatocellular carcinoma (HCC), but the high postoperative recurrence rate makes the survival benefit of patients limited. Neoadjuvant therapy mainly reduces postoperative recurrence by controlling micrometastasis and reducing preoperative tumor load and other high recurrence risk factors, but there are limited data on its application in liver cancer. Tislelizumab, a PD-1 monoclonal antibody, has shown promising efficacy with acceptable safety profile in combination with lenvatinib in the first-line treatment of advanced HCC. This study aims to explore the safety and feasibility of tislelizumab combined with lenvatinib in the neoadjuvant therapy and adjuvant therapy of resectable HCC. Methods: This prospective, single-center, single-arm phase II study (NCT04834986) enrolled patients with histologically confirmed resectable HCC who were at high risk of recurrence, as assessed by the investigators before surgery. Patients did not have any medical treatment in the past, with ECOG of 0-1, and had adequate organ and bone marrow function. Eligible patients received 4 cycles with tislelizumab (200mg, d1, Q3W) combined with Lenvatinib (8mg/kg, PO, qd) and surgery was performed within 4 weeks after treatment. At 4-8 weeks after surgery, adjuvant therapy was started with tislelizumab (200mg, d1, Q3W) and lenvatinib (8mg/kg, PO, qd) for at least half a year or until disease progression or intolerance of adverse reactions. Primary endpoints were safety and feasibility; secondary endpoints were ORR, 1 and 2-years DFS%, pCR, and DFS. Results: From Sep 7,2021 to Nov 9,2022, 24 patients (median age, 57.5 years) were enrolled, with most patients were males (95.8%) and 22 patients (91.7%) had HBV infection. All patients had Child-Pugh grade A and ECOG PS 0. The median treatment period was 4 cycles. In 24 patients, 17 patients (70.8%) underwent R0 resection, 3 patients (3/17, 17.6%) achieved complete pathological response (PCR), and 6 patients (6/17, 35.3%) achieved major pathological response rate (MPR, necrosis &gt; 70%). 3 patients (12.5%) had significant tumor shrinkage and refused surgery. 1 patient (4.2%) is waiting surgery. 3 patients (12.5%) developed disease progression. According to RECIST1.1, ORR was 54.2% (13/24, CR 1, PR 12), DCR was 87.5%. According to mRECIST, ORR was 75.0% (18/24, CR 6, PR 12), DCR was 87.5%. No grade 3 or above adverse events were observed during neoadjuvant treatment period. The most common adverse events of any grade were rash (14/24,58.3%), hypertension (5/24,20.8%) and diarrhea (4/24,16.7%). Conclusions: Tislelizumab in combination with lenvatinib was well tolerated and showed promising efficacy as a neoadjuvant therapy for resectable HCC with high risk of recurrence. Clinical trial information: NCT04834986 .
Survival outcomes of micropapillary versus classic variant, loco-regional bladder cancer: A 2004-2019 National Cancer Database analysis.
Authors: Rohan Garje, Ahmad Ozair, Anshul Saxena, Mukesh Roy, Pushan Prabhakar, Muni B. Rubens, Atulya Aman Khosla, Antonio F. Muina, Kristen F. Millado, Bruno R. Bastos, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2023)

4592 Background: Micropapillary (MP) is a rare histologic variant of urothelial cancer (UC) with luminal-type characteristics and p53-like gene expression, leading to chemotherapy resistance and poor prognosis. However, contemporary outcomes of MP variant T2-T4, N0-N1 loco-regional bladder UC after definitive therapy are underreported, which this work sought to determine. Methods: A retrospective review was performed of all eligible cases of MP and classic UC (CUC) available during 2004-2019 from National Cancer Database. Socio-demographic, pathological, and clinical attributes were analyzed via descriptive and comparative statistics. Propensity-score matching was performed to adjust for baseline differences between MP and CUC. Overall survival, being the primary outcome, was compared using multivariable Cox proportional-hazards modeling and visualized through Kaplan-Meier curves. Results: 30072 cases of CUC and 397 of MP were identified. After propensity-score matching, 395 patients remained in both groups, with matched cohorts having no baseline differences in age, sex, race, Charlson-Deyo comorbidity index (CCI), insurance status, income, distance to hospital, hospital location, rural versus urban residence, tumor pathological grade, proportion receiving radiotherapy, and proportion getting regional lymph node surgery. In both matched cohorts there were 313 males (79%) and 82 females (21%). Both cohorts had 334 (85%) T2 cases, 41 (10%) T3 cases, and 20 (5%) T4 cases. Both cohorts had 375 (95%) N0 cases and 20 (5%) N1 cases. MP variant was associated with inferior survival compared to CUC (HR 1.26, 95%CI 1.03-1.54, P=0.024). Older age (≥65 years) and higher CCI were also associated with inferior survival. Irrespective of histology, patients undergoing surgery (S) plus chemotherapy (C) had better survival compared to S alone (HR 0.77, 95%CI 0.62-0.94, P=0.012). Regional lymph node surgery resulted in improved survival (HR 0.59, 95%CI 0.42-0.83, P=0.002). Sex, race, insurance, income, and hospital type did not impact survival. Median and two-year OS are summarized. Conclusions: Survival outcomes of MP are poorer than CUC of bladder. Surgery combined with perioperative chemotherapy was associated with better survival compared to surgery alone in patients with MP and CUC. Studies evaluating novel immunotherapies and antibody drug conjugates in perioperative setting are needed to improve outcomes. [Table: see text]
Alternative allele frequency recallibration after NGS data analysis.
Authors: Maxim Ivanov, Valentina Yakushina, Mikhail Fedyanin
Journal: Journal of Clinical Oncology (2023)

3077 Background: With the spread of NGS in routine clinical practice data analysis methods actively evolve to increase and refine information yield. Not much attention is given to variant allele fraction (VAF) estimation though it impacts clinical insignificance of subclonal somatic variants and identification of variant origin. Methods: Real-world sequencing data of 2379 samples (including 781 tumor-only and 1598 blood-only sequencing datasets) obtained via amplicon-based sequencing was used for the retrospective analysis of variant allele frequency estimation of identified genetic variants employing different methods including ITVC, SiNVICT, Mutect2 and SGA. Original method (AODvAF) utilizing alignment-free algorithm based on wild-type and alternative genome subsequence abundance estimation was developed and compared with the original output from NGS data analysis software. Anticipated VAF estimation was based on analyte type and database annotation. Results: Across 3447 identified potentially germline variations (PGV) VAF estimations provided by ITVC, SiNVICT and SGA were highly correlated (Pearson correlation coefficient [PCC] 1.00), while Mutect2 and AODvAF demonstrated discordant results (Mutect2/AODvAF vs ITVC PCC 0.87/0.82). VAF miscalculation defined by absolute difference between estimated and anticipated VAF of 10% and more was noted for 25%, 26%, 22%, 15% and 7% for ITVC, SiNVICT, SGA, Mutect2 and AODvAF respectively. Across 308 pathogenic BRCA1, BRCA2, PALB2 mutations identified in blood-only sequencing 25, 15, 16, 10 and 5 were characterized by VAF of 30% and lower based on ITVC, SiNVICT, SGA, Mutect2 and AODvAF estimations respectively (54, 49, 33, 51 and 9 for VAF 40% and lower), which may lead to misinterpretation of these variants as post-zygotic. Automatic in-silico annotation of variant origin (germline vs somatic) based on ISOWN was correct for 89%, 91%, 94%, 93% and 98% of these variants. Variant origin for 55 pathogenic variants of genes associated with hereditary cancer syndromes identified in tumor-only sequencing was verified by Sanger sequencing. Cohen's kappa coefficient for variant origin discrimination (Sanger vs in-silico prediction) was 0.91, 0.90, 0.91, 0.94 and 0.97 based on VAF provided by ITVC, SiNVICT, SGA, Mutect2 and AODvAF respectively. Conclusions: Accurate VAF calculation allows precise variant origin identification and impacts interpretation of variants. Developed method allows correction of VAF after NGS data core analysis.